Anyone familiar with the clinical trial RMC-6236? Or how to enroll?

@mnewland99 , I think the trial you're referring to is https://www.clinicaltrials.gov/study/NCT06625320, described on the COH search page for Protocol No. 24607 as:

"Title: RASolute 302: A Phase 3 Multicenter, Open-label, Randomized Study of RMC-6236 versus Investigator's Choice of Standard of Care Therapy in Patients with Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)"

I'm not willing to take the chance of being randomized.

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@gamaryanne , It was actually Dr. Kim who told me I didn't qualify for his trial. He's got me on the waiting list for another possible KRAS trial (different drug, different manufacturer) in 3-4 months.

My MRI showed notable progression since March, and my CA19-9 has gone from low 60's in March to 700 this week, so I'm scrambling , counting frequent-flier miles, and casting the nets a bit farther out, hoping to find something before Dr. Kim comes through.

My only known actionable targets remain the ATM and KRAS G12D mutations, and the expression of TROP2 (for which the last trial failed). I could possibly get a PARP inhibitor to nibble away at ATM, but my primary oncologist is pretty skeptical about its value.

Thanks again to both of you for the leads.

I get about not being a fan of randomized. I also chose not to take that path. Have you had any recent scans to find any new growths? This time pain on my right side was an indicator before my CA19-9 started rising sharply. As you well know, you have to know where new growth is, if any, to know your most effective line of treatment. CT was done, but drs couldn’t tell what was inflammation from my past radiation or what was new, so they ordered PET and laid the 2 images on top of each other to get a result. I asked another dr for MRI; so we had all three and just prior I got angiogram CT of my lungs as a follow up on a benign nodule I had.
New growth in liver again, though they said they cant Gus one it’s not anywhere else based on my high CA19-9 they said. I wish they would do ERCP, but they don’t think it’s necessary. I’ve decided to the Naliri. Have you researched it yet? I hope it’s an option for you. I’m very curious what you said about PARP to “nibble” away at the ATM - that is new information for me. As always, my friend, God’s guidance in decision making of your next step.

I definitely have some small new tumors on the MRI 2 weeks ago, and one in the upper right abdominal quadrant that has grown quite a bit since the February MRI.

PARP inhibitors have been approved in pancreatic cancer patients with BRCA1, BRCA, and PALB mutations. These are related to DNA Damage Repair/Response (DDR), which they share with ATM, but not exactly (single-strand breaks vs double-strand breaks, iirc). Approval for the first three was based on a study (sorry, no link today) that found PARPi effective for them, but not for ATM. Nonetheless, that approval at least allows it to be tried off-label.

Although studies like that mainly report on a full population's response, you rarely know how an individual patient responded; everyone is different, and there could always be an outlier who responds well. I was encouraged when I read this report: https://pmc.ncbi.nlm.nih.gov/articles/PMC10953106/ about a germline ATM-mutated patient with gastric (stomach, not pancreas) cancer who received treatment with Olaparib. He responded quite well, and I followed up to confirm the patient is still alive. He eventually lost his response to Olaparib, so they added Lonsurf, and is still doing well with mild elevation of CA19-9 and small peritoneal met recurrence.

I haven't done much research on Naliri, but it's basically just a new formulation of irinotecan. My understanding is that it has a (lipid?) layer that keeps it from being broken down in the body during chemo, so that a higher concentration of it goes into the tumor cells.

Since irinotecan is one of the ingredients in Folfirinox, which didn't seem to do much in my pre-Whipple neoadjuvant therapy, I remain a little skeptical about it. Coupling that with the cost, the diarrhea reports, the 46-hour 5FU takehome pump that usually accompanies it, and the potential to disqualify me from other trials has led me to defer it until other options are exhausted.

As noted above, everyone is different, and I hope you are one of the exceptional responders!

@markymarkfl
Wondering if you would be a candidate for histotripsy to clear the liver? Esp if they are in one area.
I am on Naliri. They can add the ox if you choose that. I did not.
My ca19-9 fell from 683 to 94 after 5 treatments.
The diarrhea isn’t castastrophic in nature, but bowels to stay loose. I manage it by eating small portions at a time with some fiber (if I remember-and not too much!).
StageIv survivor on here has your mutations and did the inhibitor you are mentioning I believe. It was successful. But we are all distinctive in our cases-metastases, mutations, etc.
lastly, which center treats you in FL?

Looking for more feedback on RMC-6236 experiences? Tumor shrinkage? Length of treatment? I am trying to enroll in a Phase II trial if I can get in, want to avoid Phase III since as I understand it it is randomized between RMC-6236 and standard of care. Really appreciate hearing from you all out there!

I have not. Is that a KRAS inhibitor ?

I've been thinking I need to write to you to see how you are doing. Did you try the Naliri chemo treatment yet?

I'd hate to see you get phase 2, when researchers are already on phase 3. Naliri is the chemo drug you could get if you don't get the actual 6236 med. Ask the study oncologist if they could ensure you get Naliri if you don't get the actual drug. I myself can't tolerate Naleri, but that's only due to my underlying breathing and underlying problems; but it's an effective defender based on what other members are posting.

Hi @mnewland99! I've been thinking about you too. I've had one infusion of Naliri so far, side effects minimal. As far as I understand it, Phase II and Phase III are the same RMC-6236 drug, just the protocol is different. I would have to have 3 biopsies. Waiting to hear if I can get in at Dana Farber, short flight from my home in Ottawa Canada. How are you doing?

Also, all my doctors are advising against histotripsy. They all favor systemic therapy. Might be that my metastases have progressed too far 5.2 cm in liver, lymph node) for histotripsy to be useful. So I'm on Naliri for now. They all do recommend RMC-6236 if I can get into a trial. Also, I am KRAS G12V, and apparently Revolution Medicine are working on a drug targeting G12V, but it's going to be awhile before they get into trials, maybe a year. RMC-5217.